What is an Addisonian crisis and what are its clinical signs and symptoms?

What is Addison's Crisis and Its Signs and Symptoms

Addison's crisis (adrenal crisis) is an acute, life-threatening emergency caused by severe adrenocortical insufficiency that requires immediate recognition and treatment with intravenous hydrocortisone and aggressive fluid resuscitation—even mild symptoms like nausea can rapidly progress to shock and death within hours if untreated. 1, 2

Definition and Pathophysiology

Addison's crisis represents acute adrenocortical failure occurring when the body's cortisol demand exceeds available supply, typically in patients with underlying adrenal insufficiency exposed to physiologic stress. 1, 2 This is primarily a state of combined glucocorticoid and mineralocorticoid deficiency (in primary adrenal insufficiency), leading to cardiovascular collapse, severe volume depletion, and metabolic derangements. 1, 3

Cardinal Clinical Signs and Symptoms

Cardiovascular Manifestations

• Hypotension (often severe, <90/60 mmHg) progressing to shock is the hallmark finding. 1, 4
• Orthostatic hypotension develops before supine hypotension—monitor both sitting/standing and supine blood pressure as an early warning sign. 1
• Progressive loss of vasomotor tone occurs due to impaired alpha-adrenergic receptor responsiveness. 1
• Cardiovascular collapse and circulatory shock in advanced cases. 1, 4

Gastrointestinal Symptoms

• Severe nausea and vomiting are extremely common presenting features. 1, 4
• Abdominal pain that can mimic an acute surgical abdomen. 1, 4
• Diarrhea may accompany vomiting, contributing to volume depletion. 5

Neurological Manifestations

• Altered mental status ranging from non-specific malaise and fatigue to confusion, obtundation, and coma. 1, 4
• Impaired cognitive function and loss of consciousness in severe cases. 1, 4
• Drowsiness and somnolence are early warning signs. 1, 2

Musculoskeletal Symptoms

• Muscle pain and cramps are characteristic features. 1, 4
• Joint pain may be present. 2

Volume Status

• Severe dehydration is a key pathophysiologic feature due to mineralocorticoid deficiency causing renal sodium loss. 1, 4

Dermatologic Signs

• Hyperpigmentation of skin (in primary adrenal insufficiency) due to elevated ACTH levels—this is a chronic sign, not acute. 1, 4

Laboratory Findings

Electrolyte Abnormalities

• Hyponatremia is present in approximately 90% of newly presenting cases—the most common laboratory finding. 1
• Hyperkalemia occurs in approximately 50% of patients (its absence does not exclude the diagnosis). 1
• Metabolic acidosis due to impaired renal function and aldosterone deficiency. 1

Renal Function

• Increased creatinine and BUN from prerenal renal failure secondary to volume depletion. 1, 4

Glucose and Calcium

• Hypoglycemia is common in children but less frequent in adults. 1
• Mild to moderate hypercalcemia occurs in 10-20% of patients. 1, 4

Hormonal Findings

• Serum cortisol <250 nmol/L with markedly elevated plasma ACTH confirms primary adrenal insufficiency. 1
• Normal or even elevated cortisol levels do not exclude relative adrenal insufficiency in physiologically stressed patients. 1

Most Common Precipitating Factors

Understanding triggers is critical for prevention:

• Gastrointestinal illness with vomiting/diarrhea is the single most common precipitant—patients cannot absorb oral medications when they need them most. 6, 1, 7
• Infections of any type (respiratory, urinary, systemic). 1, 7
• Surgical procedures performed without adequate steroid coverage. 1, 7
• Physical trauma or injuries. 1, 7
• Abrupt discontinuation of chronic glucocorticoid therapy. 8, 5
• Myocardial infarction and severe allergic reactions. 1, 7
• Failure to increase glucocorticoid doses during intercurrent illness despite patient education. 6

Critical Clinical Pearls

• Symptoms can develop from robust health to life-threatening crisis within hours—do not underestimate the rapidity of deterioration. 2
• Even a mild upset stomach may precipitate crisis because patients cannot absorb their oral replacement medication. 6, 1
• Persistent fever may be due to adrenal insufficiency itself, not just infection—do not reduce steroids while the patient remains febrile. 1
• Consider adrenal crisis in any patient with unexplained collapse, hypotension, vomiting, or diarrhea, especially with electrolyte abnormalities. 1
• The absence of hyperkalemia does not exclude the diagnosis—it is present in only 50% of cases. 1
• Patients on prednisolone or prednisone for other conditions are NOT protected from adrenal crisis because these agents have minimal mineralocorticoid activity. 3
• ECG changes (ST depression, inverted T waves) may mimic cardiac ischemia without actual coronary disease. 9

Special Populations at Risk

• Patients with chronic under-replacement of fludrocortisone combined with low salt intake. 6, 1
• Patients on immune checkpoint inhibitors who develop hypophysitis, especially during rapid corticosteroid tapers. 1
• Patients with underlying psychiatric disorders affecting medication adherence. 6, 1
• Patients starting thyroid hormone replacement before adequate glucocorticoid replacement (can trigger crisis). 1